The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation.